Crucial role of the amino-terminal tyrosine residue 42 and the carboxyl-terminal PEST domain of IκBα in NF-κB activation by an oxidative stress
Open accessAbstract
Activation of transcription factor NF-κB involves the signal-dependent degradation of basally phosphorylated inhibitors such as IκBα. In response to proinflammatory cytokines or mitogens, the transduction machinery has recently been characterized, but the activation mechanism upon oxidative stress remains unknown. In the present work, we provide several lines of evidence that NF-κB activation in a T lymphocytic cell line (EL4) by hydrogen peroxide (H2O2) did not involve phosphorylation of the serine residues 32 and 36 in the amino-terminal part of IκBα. Indeed, mutation of Ser32 and Ser36 blocked IL-1β- or PMA-induced NF-κB activation, but had no effect on its activation by H2O2. Although IκBα was phosphorylated upon exposure to H2O2, tyrosine residue 42 and the C-terminal PEST (proline-glutamic acid-serine-threonine) domain played an important role. Indeed, mutation of tyrosine 42 or serine/threonine residues of the PEST domain abolished NF-κB activation by H2O2, while it had no effect on activation by IL-1β or PMA-ionomycin. This H2O2-inducible phosphorylation was not dependent on IκB kinase activation, but could involve casein kinase II, because an inhibitor of this enzyme (5,6-dichloro-1-β-d-ribofuranosyl-benzimidazole) blocks NF-κB activation. H2O2-induced IκBα phosphorylation was followed by its degradation by calpain proteases or through the proteasome. Taken together, our findings suggest that NF-κB activation by H2O2 involves a new mechanism that is totally distinct from those triggered by proinflammatory cytokines or mitogens.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
H2O2 induces activation of nuclear factor NF-κβ, including tyrosine phosphorylation of IkB and activation of IKK.
“H2O2 induces activation of factor nuclear NF-κβ (the factor that controls DNA transcription), including tyrosine phosphorylation of IkB and activation of IKK [77].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [77]
Exogenous H2O2 or induction of H2O2 release by IL1β or LPS can activate NFκB in multiple cell types, including human myeloid KBM-5 cells, human epithelial-like MCF-7 cells, mouse EL-5 T-cells and macrophages.
“Exogenous application of H2O2 or induction of H2O2 release by IL1β or LPS treatment can activate NFκB in multiple cell types, including human myeloid KBM-5 cells, human epithelial-like MCF-7 cells, mouse EL-5 T-cells and macrophages [143,144,145,146].”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [143]
H2O2-mediated NFκB activation results from phosphorylation of IκB tyrosine residues.
“Multiple studies have shown that H2O2-mediated NFκB activation results from phosphorylation of IκB tyrosine residues [143,144].”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [143]
H2O2-mediated NFκB activation does not involve degradation of IκB.
“However, this process does not involve the degradation of IκB, which is controlled by IκB kinase (IKK)-mediated serine phosphorylation.”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [143]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
NF-κB AND REL PROTEINS: Evolutionarily Conserved Mediators of Immune Responses
Ghosh, S., May, M. J., & Kopp, E. B. (1998) · Annual Review of Immunology · doi:10.1146/annurev.immunol.16.1.225 · Cited by 5,182 · see citing works
Function and Activation of NF-kappaB in the Immune System
Baeuerle, P. A., & Henkel, T. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.001041 · Cited by 4,745 · see citing works
Schreck, R., RIEBER, P., & Baeuerle, P. A. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07761.x · Cited by 3,816 · see citing works
Baeuerle, P. A., & Baltimore, D. (1996) · Cell · doi:10.1016/s0092-8674(00)81318-5 · Cited by 3,002 · see citing works
A cytokine-responsive IκB kinase that activates the transcription factor NF-κB
DiDonato, J. A., Hayakawa, M., Rothwarf, D. M., Zandi, E., & Karin, M. (1997) · Nature · doi:10.1038/41493 · Cited by 2,125 · see citing works
Structure, Regulation and Function of NF-kappaB
Siebenlist, U. K., Franzoso, G., & Brown, K. D. (1994) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.10.110194.002201 · Cited by 2,086 · see citing works
IKK-1 and IKK-2: Cytokine-Activated IκB Kinases Essential for NF-κB Activation
Mercurio, F., Zhu, H., Murray, B. W., Shevchenko, A., Bennett, B. L., Li, J. W., Young, D. B., Barbosa, M. S., Mann, M., Manning, A. M., et al. (1997) · Science · doi:10.1126/science.278.5339.860 · Cited by 2,042 · see citing works
Identification and Characterization of an IκB Kinase
Régnier, C. H., Song, H. Y., Gao, X., Goeddel, D. V., Cao, Z., & Rothe, M. (1997) · Cell · doi:10.1016/s0092-8674(00)80344-x · Cited by 1,176 · see citing works
REDOX REGULATION OF CELLULAR ACTIVATION
Nakamura, H., Nakamura, K., & Yodoi, J. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.351 · Cited by 1,106 · see citing works
The I kappa B proteins: multifunctional regulators of Rel/NF-kappa B transcription factors.Preprint
Beg, A. A., & Baldwin, A. S. (1993) · Genes & Development · doi:10.1101/gad.7.11.2064 · Cited by 803 · see citing works
Is NF-kappaB the sensor of oxidative stress?
Li, N., & Karin, M. (1999) · PubMed · Cited by 786 · see citing works
Haskill, S., Beg, A. A., Tompkins, S. M., Morris, J. S., Yurochko, A. D., Sampson-Johannes, A., Mondal, K., Ralph, P., & Baldwin, A. S. (1991) · Cell · doi:10.1016/0092-8674(91)90022-q · Cited by 732 · see citing works
Is NF‐κB the sensor of oxidative stress?
Li, N., & Karin, M. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.10.1137 · Cited by 702 · see citing works
Tyrosine Phosphorylation of IκB-α Activates NF-κB without Proteolytic Degradation of IκB-α
Imbert, V., Rupec, R. A., Livolsi, A., Pahl, H. L., Traenckner, E. B.-M., Mueller‐Dieckmann, C., Farahifar, D., Rossi, B., Auberger, P., Baeuerle, P. A., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)80153-1 · Cited by 660 · see citing works
The O2−-forming NADPH oxidase of the phagocytes: nature, mechanisms of activation and function
Rossi, F. (1986) · Biochimica et Biophysica Acta (BBA) - Reviews on Bioenergetics · doi:10.1016/0304-4173(86)90005-4 · Cited by 656 · see citing works
Meier, B., Radeke, H. H., Selle, S., Younes, M., Sies, H., Resch, K., & Habermehl, G. (1989) · Biochemical Journal · doi:10.1042/bj2630539 · Cited by 650 · see citing works
The Beginning of the End: IκB Kinase (IKK) and NF-κB Activation
Karin, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.39.27339 · Cited by 640 · see citing works
The superoxide‐generating oxidase of phagocytic cells
Morel, F., Doussière, J., & Vignais, P. V. (1991) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1991.tb16312.x · Cited by 562 · see citing works
Song, H. Y., Régnier, C. H., Kirschning, C. J., Goeddel, D. V., & Rothe, M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.18.9792 · Cited by 554 · see citing works
Functions of glutathione and glutathione disulfide in immunology and immunopathology
Dröge, W., Schulze‐Osthoff, K., Mihm, S., Galter, D., Schenk, H., Eck, H., Roth, S., & Gmünder, H. (1994) · The FASEB Journal · doi:10.1096/fasebj.8.14.7958618 · Cited by 444 · see citing works
Ionizing radiation and short wavelength UV activate NF-κB through two distinct mechanisms
Li, N., & Karin, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.13012 · Cited by 429 · see citing works
Calpain: A Protease in Search of a Function?
Carafoli, E., & Molinari, M. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8378 · Cited by 356 · see citing works
Li, J., Feng, W., Gallup, M., Kim, J.-H., Gum, J. R., Kim, Y., & Basbaum, C. B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.10.5718 · Cited by 333 · see citing works
Bridging the Gap: Composition, Regulation, and Physiological Function of the IκB Kinase Complex
Zandi, E., & Karin, M. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.7.4547 · Cited by 321 · see citing works
p105 and p98 precursor proteins play an active role in NF-kappa B-mediated signal transduction.Preprint
Mercurio, F., DiDonato, J. A., Rosette, C., & Karin, M. (1993) · Genes & Development · doi:10.1101/gad.7.4.705 · Cited by 282 · see citing works
Miyamoto, S., & Verma, I. M. (1995) · Advances in cancer research · doi:10.1016/s0065-230x(08)60257-2 · Cited by 278 · see citing works
Schieven, G. L., Kirihara, J. M., Myers, D. E., Ledbetter, J. A., & Uckun, F. M. (1993) · Blood · doi:10.1182/blood.v82.4.1212.1212 · Cited by 264 · see citing works
Low levels of reactive oxygen species as modulators of cell function
Remacle, J., Raes, M. J., Toussaint, O., Renard, P., & Rao, G. (1995) · Mutation Research/DNAging · doi:10.1016/0921-8734(95)90004-7 · Cited by 254 · see citing works
Tumor Necrosis Factor-α-inducible IκBα Proteolysis Mediated by Cytosolic m-Calpain
Han, Y., Weinman, S. A., Boldogh, I. R., Walker, R. K., & Brasier, A. R. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.2.787 · Cited by 241 · see citing works
IκBα is a target for the mitogen‐activated 90 kDa ribosomal S6 kinase
Schouten, G. J., Vertegaal, A. C. O., Whiteside, S. T., Israël, A., Toebes, M., Dorsman, J. C., van der Eb, A. J., & Zantema, A. (1997) · The EMBO Journal · doi:10.1093/emboj/16.11.3133 · Cited by 225 · see citing works
Sequential DNA damage‐independent and ‐dependent activation of NF‐κB by UV
Bender, K., Göttlicher, M., Whiteside, S. T., Rahmsdorf, H. J., & Herrlich, P. (1998) · The EMBO Journal · doi:10.1093/emboj/17.17.5170 · Cited by 223 · see citing works
The PEST Domain of IκBα Is Necessary and Sufficient forin Vitro Degradation by μ-Calpain
Shumway, S. D., Maki, M., & Miyamoto, S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.43.30874 · Cited by 202 · see citing works
Lin, R., Beauparlant, P., Makris, C., Meloche, S., & Hiscott, J. B. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.4.1401 · Cited by 198 · see citing works
Delić, J., Masdehors, P., Ōmura, S., Cosset, J.-M., Dumont, J., Binet, J. L., & Magdelénat, H. (1998) · British Journal of Cancer · doi:10.1038/bjc.1998.183 · Cited by 195 · see citing works
McElhinny, J. A., Trushin, S. A., Bren, G. D., Chester, N., & Payá, C. V. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.899 · Cited by 187 · see citing works
In vitro and in vivo inhibition of cysteine proteinases by EST, a new analog of E-64.
Tamai, M., Matsumoto, K., OMURA, S., Koyama, I., Ozawa, Y., & Hanada, K. (1986) · Journal of Pharmacobio-Dynamics · doi:10.1248/bpb1978.9.672 · Cited by 174 · see citing works
Schwarz, E. M., Antwerp, D. V., & Verma, I. M. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.7.3554 · Cited by 163 · see citing works
ACTIVATION OF NF‐KB IN HUMAN SKIN FIBROBLASTS BY THE OXIDATIVE STRESS GENERATED BY UVA RADIATION
Vile, G. F., Tanew‐Iliitschew, A., & Tyrrell, R. M. (1995) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1995.tb02369.x · Cited by 154 · see citing works
Both Amino- and Carboxyl-Terminal Sequences within IκBα Regulate Its Inducible Degradation
Sun, S., Elwood, J., & Greene, W. C. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.1058 · Cited by 152 · see citing works
Yoshida, S., Katoh, T., Tetsuka, T., Uno, K., Matsui, N., & Okamoto, T. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.1.351 · Cited by 149 · see citing works
Phosphorylation of IκB-α Inhibits Its Cleavage by Caspase CPP32 in Vitro
Barkett, M., Xue, D., Horvitz, H. R., & Gilmore, T. D. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.47.29419 · Cited by 145 · see citing works
Yoshida, S., Katoh, T., Tetsuka, T., Uno, K., Matsui, N., & Okamoto, T. (1999) · PubMed · Cited by 143 · see citing works
Control of gene expression by proteolysis
Pahl, H. L., & Baeuerle, P. A. (1996) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(96)80007-x · Cited by 143 · see citing works
Activation of the NF-κB transcription factor in a T-lymphocytic cell line by hypochlorous acid
Schoonbroodt, S., Legrand-Poels, S., Best‐Belpomme, M., & Piette, J. G. (1997) · Biochemical Journal · doi:10.1042/bj3210777 · Cited by 143 · see citing works
Self-citationBonizzi, G., Piette, J. G., Merville, M. P., & Bours, V. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.11.5264 · Cited by 142 · see citing works
Self-citationMiyoshi, H., Umeshita, K., Sakon, M., Imajoh‐Ohmi, S., Fujitani, K., Gotoh, M., Oiki, E., Kambayashi, J., & Monden, M. (1996) · Gastroenterology · doi:10.1053/gast.1996.v110.pm8964416 · Cited by 141 · see citing works
Dejardin, E., Bonizzi, G., Bellahcène, A., Castronovo, V., Merville, M.-P., & Bours, V. (1995) · PubMed · Cited by 124 · see citing works
Novel IκBα Proteolytic Pathway in WEHI231 Immature B Cells
Miyamoto, S., Seufzer, B. J., & Shumway, S. D. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.1.19 · Cited by 118 · see citing works
Antwerp, D. J. V., & Verma, I. M. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.11.6037 · Cited by 90 · see citing works
Kim, S., & Kahn, R. (1997) · Biochemical Journal · doi:10.1042/bj3230621 · Cited by 76 · see citing works
Transcription Factor NF-κB Is Activated by Photosensitization Generating Oxidative DNA Damages
Legrand-Poels, S., Bours, V., Piret, B., Pflaum, M., Epe, B., Rentier, B., & Piette, J. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.12.6925 · Cited by 70 · see citing works
Self-citationCalpain Contributes to Silica-Induced IκB-α Degradation and Nuclear Factor-κB Activation
Chen, F., Lu, Y., Kuhn, D. C., Maki, M., Shi, X., Sun, S., & Demers, L. M. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1997.0132 · Cited by 68 · see citing works
Bonizzi, G., Dejardin, E., Piret, B., Piette, J. G., Merville, M., & Bours, V. (1996) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1996.0544r.x · Cited by 67 · see citing works
Self-citationPlasma membrane calcium pump: structure, function and relationships
Carafoli, E. (1997) · Basic Research in Cardiology · doi:10.1007/bf00794069 · Cited by 56 · see citing works
Kretz‐Remy, C., Bates, E. E. M., & Arrigo, A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.6.3180 · Cited by 52 · see citing works
Piret, B., Legrand-Poels, S., Sappey, C., & Piette, J. G. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.tb20283.x · Cited by 47 · see citing works
Self-citationHeilker, R., Freuler, F., Pulfer, R., Padova, F. D., & Eder, J. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00028.x · Cited by 45 · see citing works
Zandomeni, R. O. (1989) · Biochemical Journal · doi:10.1042/bj2620469 · Cited by 39 · see citing works
The Role of the C-terminal Domain of IκBα in Protein Degradation and Stabilization
Beauparlant, P., Lin, R., & Hiscott, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.18.10690 · Cited by 38 · see citing works
Dröge, W., Mihm, S., Bockstette, M., & Roth, S. (1994) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(94)34084-6 · Cited by 37 · see citing works
Zhang, J., Patel, J. M., & Block, E. R. (1998) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1998.275.3.l461 · Cited by 37 · see citing works
Mitev, V., Bayat-Sarmadi, M., Lemnaouar, M., PUISSANT, C., & Houdebine, L. (1996) · Biochemical Pharmacology · doi:10.1016/s0006-2952(96)00523-0 · Cited by 31 · see citing works
Watabe, M., Nakajo, S., Yoshida, T., Kuroiwa, Y., & Nakaya, K. (1997) · PubMed · Cited by 28 · see citing works
Phosphorylation of A170 Stress Protein by Casein Kinase II-like Activity in Macrophages
Yanagawa, T., Yuki, K., Yoshida, H., Bannai, S., & Ishii, T. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7783 · Cited by 24 · see citing works
Calcium-Dependent Proteolysis in Rabbit Lens Epithelium after Oxidative Stress
Andersson, M., Sjöstrand, J., Petersen, A. H., & Karlsson, J. (1998) · Ophthalmic Research · doi:10.1159/000055469 · Cited by 15 · see citing works
Flagged first, then by citations
1 of the 66 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Free Radicals in the Physiological Control of Cell Function
Dröge, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00018.2001 · Cited by 9,855 · see citing works
Crosstalk of reactive oxygen species and NF-κB signaling
Morgan, M. J., & Liu, Z.-G. (2011) · Cell Research · doi:10.1038/cr.2010.178 · Cited by 3,505 · see citing works
Cellular response to oxidative stress: Signaling for suicide and survival *
Martindale, J., & Holbrook, N. (2002) · Journal of Cellular Physiology · doi:10.1002/jcp.10119 · Cited by 2,392 · see citing works
Reactive Oxygen Species in Metabolic and Inflammatory Signaling
Forrester, S. J., Kikuchi, D. S., Hernandes, M. S., Xu, Q., & Griendling, K. K. (2018) · Circulation Research · doi:10.1161/circresaha.117.311401 · Cited by 2,081 · see citing works
Ros and ros-mediated cellular signaling
Zhang, J., Wang, X., Vikash, V., Ye, Q., Wu, D., Liu, Y., & Dong, W. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/4350965 · Cited by 1,980 · see citing works
NF-κB activation by reactive oxygen species: Fifteen years later
Gloire, G., Legrand-Poels, S., & Piette, J. G. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.04.011 · Cited by 1,540 · see citing works
Self-citationPhosphorylation of NF-κB and IκB proteins: implications in cancer and inflammation
Viatour, P., Merville, M., Bours, V., & Chariot, A. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.11.009 · Cited by 1,497 · see citing works
Simpson, D. S. A., & Oliver, P. L. (2020) · Antioxidants · doi:10.3390/antiox9080743 · Cited by 1,044 · see citing works
“Multiple studies have shown that H2O2-mediated NFκB activation results from phosphorylation of IκB tyrosine residues [143,144].”
BackgroundA subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1
Pillay, J., Kamp, V. M., van Hoffen, E., Visser, T., Tak, T., Lammers, J. J., Ulfman, L. H., Leenen, L. P. H., Pickkers, P., & Koenderman, L. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57990 · Cited by 829 · see citing works
The role of oxidative stress during inflammatory processes
Lugrin, J., Rosenblatt‐Velin, N., Parapanov, R., & Liaudet, L. (2013) · Biological Chemistry · doi:10.1515/hsz-2013-0241 · Cited by 742 · see citing works
NF-κB: pivotal mediator or innocent bystander in atherogenesis?
Collins, T., & Cybulsky, M. I. (2001) · Journal of Clinical Investigation · doi:10.1172/jci10373 · Cited by 727 · see citing works
Perkins, N. D. (2006) · Oncogene · doi:10.1038/sj.onc.1209937 · Cited by 674 · see citing works
Gong, G., Waris, G., Tanveer, R., & Siddiqui, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171311298 · Cited by 580 · see citing works
Basic Principles and Emerging Concepts in the Redox Control of Transcription Factors
Brigelius-Flohé, R., & Flohé, L. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3534 · Cited by 577 · see citing works
Redox signaling in macrophages.
Forman, H., & Torres, M. (2001) · Molecular Aspects of Medicine · doi:10.1016/s0098-2997(01)00010-3 · Cited by 539 · see citing works
Takada, Y., Mukhopadhyay, A., Kundu, G. C., Mahabeleshwar, G. H., Singh, S., & Aggarwal, B. B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212389200 · Cited by 495 · see citing works
Good cop, bad cop: the different faces of NF-κB
Perkins, N. D., & Gilmore, T. D. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401838 · Cited by 489 · see citing works
NADPH Oxidase-Dependent Signaling in Endothelial Cells: Role in Physiology and Pathophysiology
Frey, R. S., Ushio‐Fukai, M., & Malik, A. B. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2220 · Cited by 423 · see citing works
Bubici, C., Papa, S., Dean, K., & Franzoso, G. (2006) · Oncogene · doi:10.1038/sj.onc.1209936 · Cited by 399 · see citing works
Joining the cell survival squad: an emerging role for protein kinase CK2
Ahmed, K. (2002) · Trends in Cell Biology · doi:10.1016/s0962-8924(02)02279-1 · Cited by 385 · see citing works
Waris, G., Huh, K.-W., & Siddiqui, A. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.22.7721-7730.2001 · Cited by 319 · see citing works
Bidirectional regulation of NF-κB by reactive oxygen species: A role of unfolded protein response
Nakajima, S., & Kitamura, M. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.06.020 · Cited by 315 · see citing works
Redox-Sensitive Kinases of the Nuclear Factor-κB Signaling Pathway
Pantano, C., Reynaert, N., van der Vliet, A., & Janssen-Heininger, Y. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.1791 · Cited by 302 · see citing works
Glutathione, Stress Responses, and Redox Signaling in Lung Inflammation
Rahman, I., Biswas, S. K., Jimenez, L. A., Torrès, M., & Forman, H. J. (2004) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.42 · Cited by 297 · see citing works
Shishodia, S., Potdar, P. D., Gairola, C. G., & Aggarwal, B. B. (2003) · Carcinogenesis · doi:10.1093/carcin/bgg078 · Cited by 292 · see citing works
Macrophage Signaling and Respiratory Burst
Iles, K. E., & Forman, H. J. (2002) · Immunologic Research · doi:10.1385/ir:26:1-3:095 · Cited by 290 · see citing works
Role of Hydrogen Peroxide in NF-κB Activation: From Inducer to Modulator
Oliveira-Marques, V., Marinho, H. S., Cyrne, L., & Antunes, F. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2601 · Cited by 278 · see citing works
Anto, R. J. (2002) · Carcinogenesis · doi:10.1093/carcin/23.9.1511 · Cited by 278 · see citing works
Rodríguez‐Iturbe, B., Vaziri, N. D., Herrera-Acosta, J., & Johnson, R. J. (2004) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00269.2003 · Cited by 277 · see citing works
Oxidative stress in the pathogenesis of psoriasis
Zhou, Q., Mrowietz, U., & Rostami‐Yazdi, M. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.06.033 · Cited by 274 · see citing works
The Cadherin Cytoplasmic Domain Is Unstructured in the Absence of β-Catenin
Huber, A. H., Stewart, D. B., Laurents, D. V., Nelson, W. J., & Weis, W. I. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010377200 · Cited by 268 · see citing works
Pianetti, S., Arsura, M., Romieu, R., Coffey, R. J., & Sonenshein, G. E. (2001) · Oncogene · doi:10.1038/sj.onc.1204257 · Cited by 265 · see citing works
Transcriptional responses to oxidative stress: Pathological and toxicological implications
Ma, Q. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.11.004 · Cited by 248 · see citing works
Oxidative stress interference with the nuclear factor- κB activation pathways
Schoonbroodt, S., & Piette, J. G. (2000) · Biochemical Pharmacology · doi:10.1016/s0006-2952(00)00371-3 · Cited by 240 · see citing works
Self-citationReuse, S., Calao, M., Kabeya, K., Guiguen, A., Gatot, J., Quivy, V., Vanhulle, C., Lamine, A., Vaira, D., Demonté, D., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006093 · Cited by 239 · see citing works
Self-citationRedox Regulation of Nuclear Post-Translational Modifications During NF-κB Activation
Gloire, G., & Piette, J. G. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2463 · Cited by 220 · see citing works
Self-citationCa2+-dependent proteases in ischemic neuronal death
Yamashima, T. (2004) · Cell Calcium · doi:10.1016/j.ceca.2004.03.001 · Cited by 213 · see citing works
Korn, S. H., Wouters, E. F. �., Vos, N., & Janssen-Heininger, Y. M. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104321200 · Cited by 200 · see citing works
Regulation of gene expression by oxygen: NF-κB and HIF-1, two extremes
Michiels, C., Minet, E., Mottet, D., & Raes, M. J. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)01045-6 · Cited by 200 · see citing works
Reactive oxygen species: Role in carcinogenesis, cancer cell signaling and tumor progression
Sarmiento-Salinas, F. L., Pérez-González, A., Acosta-Casique, A., Ix-Ballote, A., Díaz, A., Treviño, S., Rosas-Murrieta, N. H., Millán-Pérez-Peña, L., & Maycotte, P. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119942 · Cited by 205 · see citing works
The effect of reactive oxygen species on the synthesis of prostanoids from arachidonic acid.
Korbecki, J., Baranowska‐Bosiacka, I., Gutowska, I., & Chlubek, D. (2013) · PubMed · Cited by 194 · see citing works
Inflammatory cause of metabolic syndrome via brain stress and NF-κB
Cai, D., & Liu, T. (2012) · Aging · doi:10.18632/aging.100431 · Cited by 189 · see citing works
Regulating the regulator: NF-κB signaling in heart
Hall, G., Hasday, J. D., & Rogers, T. B. (2006) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2006.07.006 · Cited by 183 · see citing works
Kamata, H., Manabe, T., Oka, S., Kamata, K., & Hirata, H. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02712-6 · Cited by 179 · see citing works
Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease
Yan, C., Hu, W., Tu, J., Li, J., Liang, Q., & Han, S. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04166-8 · Cited by 176 · see citing works
Chiurchiù, V., & Maccarrone, M. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3547 · Cited by 171 · see citing works
Ethyl pyruvate modulates inflammatory gene expression in mice subjected to hemorrhagic shock
Yang, R., Gallo, D. J., Baust, J., Uchiyama, T., Watkins, S. C., Delude, R. L., & Fink, M. P. (2002) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00022.2002 · Cited by 168 · see citing works
Roles of IKK kinases and protein kinase CK2 in activation of nuclear factor-kappaB in breast cancer.
Romieu, R., Landesman‐Bollag, E., Seldin, D. C., Traish, A. M., Mercurio, F., & Sonenshein, G. E. (2001) · PubMed · Cited by 160 · see citing works
Hydrogen peroxide in inflammation: Messenger, guide, and assassin
Wittmann, C., Chockley, P., Singh, S. K., Pase, L., Lieschke, G. J., & Grabher, C. (2012) · Advances in Hematology · doi:10.1155/2012/541471 · Cited by 143 · see citing works
The Role of Reactive Species on Innate Immunity
Andrés, C., Pérez de la Lastra, J., Juan, C., Plou, F., & Pérez-Lebeña, E. (2022) · Vaccines · doi:10.3390/vaccines10101735 · Cited by 142 · see citing works
Reactive Oxygen Species as Intracellular Signaling Molecules in the Cardiovascular System
Krylatov, A. V., Маслов, Л. Н., Воронков, Н. С., Boshchenko, A. A., Popov, S. V., Gomez, L., Wang, H., Jaggi, A. S., & Downey, J. M. (2018) · Current Cardiology Reviews · doi:10.2174/1573403x14666180702152436 · Cited by 142 · see citing works
NF-κB activation by double-strand breaks
Habraken, Y., & Piette, J. G. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.07.015 · Cited by 140 · see citing works
Self-citationLi, Q., Tan, Y., Chen, S., Xiao, X., Zhang, M., Wu, Q., & Dong, M. (2020) · Journal of Receptors and Signal Transduction · doi:10.1080/10799893.2020.1808675 · Cited by 136 · see citing works
Specification of DNA Binding Activity of NF- B ProteinsPreprint
Wan, F., & Lenardo, M. J. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000067 · Cited by 133 · see citing works
A Quantitative Study of NF-κB Activation by H2O2: Relevance in Inflammation and Synergy with TNF-α
Oliveira-Marques, V., Cyrne, L., Marinho, H. S., & Antunes, F. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.6.3893 · Cited by 132 · see citing works
Li, S., Ye, L., Yu, X., Xu, B., Li, K., Zhu, X., Liu, H., Wu, X., & Kong, L. (2009) · Virology · doi:10.1016/j.virol.2009.06.039 · Cited by 132 · see citing works
Lee, C.-H., Chen, J., Hsiang, C., Wu, S., Wu, H.-C., & Ho, T. (2007) · Pharmacological Research · doi:10.1016/j.phrs.2007.06.003 · Cited by 129 · see citing works
Song, M., Kellum, J. A., Kaldas, H., & Fink, M. P. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.056622 · Cited by 128 · see citing works
Waris, G., Tardif, K. D., & Siddiqui, A. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)01300-x · Cited by 127 · see citing works
Moon, P., Lee, B.-H., Jeong, H., An, H., Park, S., Kim, H., Ko, S., Um, J., Hong, S., & Kim, H. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.10.021 · Cited by 126 · see citing works
Fink, M. P. (2002) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200203000-00009 · Cited by 125 · see citing works
Čapek, J., & Roušar, T. (2021) · Molecules · doi:10.3390/molecules26164710 · Cited by 122 · see citing works
Waris, G., Livolsi, A., Imbert, V., Peyron, J., & Siddiqui, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303248200 · Cited by 117 · see citing works
RetractedQuivy, V., Adam, E., Collette, Y., Demonté, D., Chariot, A., Vanhulle, C., Berkhout, B., Castellano, R., de Launoit, Y., Burny, A., et al. (2002) · Journal of Virology · doi:10.1128/jvi.76.21.11091-11103.2002 · Cited by 117 · see citing works
Self-citationRole of reactive oxygen and nitrogen species in acute respiratory distress syndrome
Fink, M. P. (2002) · Current Opinion in Critical Care · doi:10.1097/00075198-200202000-00002 · Cited by 113 · see citing works
Nuclear Factor Kappa B Signaling Complexes in Acute Inflammation
Rius‐Pérez, S., Pérez, S., Martí‐Andrés, P., Monsalve, M., & Sastre, J. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7975 · Cited by 112 · see citing works
Intrinsic unstructuredness and abundance of PEST motifs in eukaryotic proteomes
Singh, G. P., Ganapathi, M., Sandhu, K. S., & Dash, D. (2005) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20746 · Cited by 106 · see citing works
Sappington, P. L., Han, X., Yang, R., Delude, R. L., & Fink, M. P. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.043182 · Cited by 105 · see citing works
Robbesyn, F., Garcia, V., Augè, N., Vieira, O. V., Frisach, M., Salvayre, R., & Nègre‐Salvayre, A. (2003) · The FASEB Journal · doi:10.1096/fj.02-0240fje · Cited by 105 · see citing works
Phosphorylation by the Protein Kinase CK2 Promotes Calpain-Mediated Degradation of IκBα
Shen, J., Channavajhala, P. L., Seldin, D. C., & Sonenshein, G. E. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.9.4919 · Cited by 103 · see citing works
Role for casein kinase 2 in the regulation of HIF‐1 activity
Mottet, D., Ruys, S. P. D., Demazy, C., Raes, M. J., & Michiels, C. (2005) · International Journal of Cancer · doi:10.1002/ijc.21268 · Cited by 99 · see citing works
NF-κB as a target for cancer therapy
Melisi, D., & Chiao, P. J. (2007) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.11.2.133 · Cited by 99 · see citing works
Redox regulation of macrophages
Tran, N., & Mills, E. L. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103123 · Cited by 97 · see citing works
Reelfs, O., Tyrrell, R. M., & Pourzand, C. (2004) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2004.22620.x · Cited by 92 · see citing works
Tsung, A., Kaizu, T., Nakao, A., Shao, L., Bucher, B. T., Fink, M. P., Murase, N., & Geller, D. A. (2005) · Transplantation · doi:10.1097/01.tp.0000151681.07474.2e · Cited by 91 · see citing works
Adam, E., Quivy, V., Bex, F., Chariot, A., Collette, Y., Vanhulle, C., Schoonbroodt, S., Goffin, V., Nguyên, T. L.-A., Gloire, G., et al. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.17.6200-6209.2003 · Cited by 91 · see citing works
Self-citationJaspers, I., Zhang, W., Fraser, A., Samet, J. M., & Reed, W. (2001) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.24.6.4344 · Cited by 91 · see citing works
Schaecher, K. E., Goust, J. M., & Banik, N. L. (2004) · Neurochemical Research · doi:10.1023/b:nere.0000026410.56000.dd · Cited by 89 · see citing works
Regulatory mechanisms of viral hepatitis B and C
Waris, G., & Siddiqui, A. (2003) · Journal of Biosciences · doi:10.1007/bf02970150 · Cited by 85 · see citing works
Dehydroepiandrosterone Modulates Nuclear Factor-κB Activation in Hippocampus of Diabetic Rats
Aragno, M., Mastrocola, R., Brignardello, E., Catalano, M. G., Robino, G., Manti, R., Parola, M., Danni, O., & Boccuzzi, G. (2002) · Endocrinology · doi:10.1210/en.2002-220182 · Cited by 83 · see citing works
Wuerzberger‐Davis, S. M., Nakamura, Y., Seufzer, B. J., & Miyamoto, S. (2006) · Oncogene · doi:10.1038/sj.onc.1209815 · Cited by 82 · see citing works
Degeneration of neuronal cells due to oxidative stress—microglial contribution
Koutsilieri, E., Scheller, C., Tribl, F., & Riederer, P. F. (2002) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(02)00021-4 · Cited by 81 · see citing works
Impact of Intravascular Hemolysis in Malaria on Liver Dysfunction
Dey, S., Bindu, S., Goyal, M., Pal, C., Alam, A., Iqbal, M. S., Kumar, R., Sarkar, S., & Bandyopadhyay, U. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.341255 · Cited by 79 · see citing works
Zhao, G., Jiang, K., Wu, H., Qiu, C., Deng, G., & Peng, X. (2017) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13194 · Cited by 77 · see citing works
Kustermans, G., Benna, J. E., Piette, J. G., & Legrand-Poels, S. (2005) · Biochemical Journal · doi:10.1042/bj20041318 · Cited by 75 · see citing works
Self-citationReactive Oxygen Species: A Double-Edged Sword in the Modulation of Cancer Signaling Pathway Dynamics
Nigam, M., Punia, B., Dimri, D. B., Mishra, A. P., Radu, A.-F., & Bungau, G. S. (2025) · Cells · doi:10.3390/cells14151207 · Cited by 77 · see citing works
Kamiński, M. M., Röth, D., Krammer, P. H., & Gülow, K. (2013) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-013-0235-0 · Cited by 72 · see citing works
Sendtner, N., Seitz, R., Brandl, N., Müller, M., & Gülow, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262010240 · Cited by 75 · see citing works
Neutrophils: The Role of Oxidative and Nitrosative Stress in Health and Disease
Manda‐Handzlik, A., & Demkow, U. A. (2015) · Advances in experimental medicine and biology · doi:10.1007/5584_2015_117 · Cited by 72 · see citing works
Palungwachira, P., Tancharoen, S., Phruksaniyom, C., Klungsaeng, S., Srichan, R., Kikuchi, K., & Nararatwanchai, T. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2089817 · Cited by 71 · see citing works
Interplay between BMPs and Reactive Oxygen Species in Cell Signaling and Pathology
Sánchez-de-Diego, C., Valer, J., Pimenta-Lopes, C., Rosa, J. L., & Ventura, F. (2019) · Biomolecules · doi:10.3390/biom9100534 · Cited by 63 · see citing works
Mendivil‐Perez, M., Velez‐Pardo, C., & Jiménez-Del-Río, M. (2012) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2012/313275 · Cited by 65 · see citing works
Parhar, K. K. S., Ray, A., Steinbrecher, U. P., Nelson, C. C., & Salh, B. S. (2003) · Immunology · doi:10.1046/j.1365-2567.2003.01603.x · Cited by 69 · see citing works
Systems approaches to investigate the role of NF-κB signaling in aging
Haga, M., & Okada, M. (2022) · Biochemical Journal · doi:10.1042/bcj20210547 · Cited by 66 · see citing works
Large hepatitis delta antigen activates STAT‐3 and NF‐κB via oxidative stress
Williams, V., Brichler, S., Khan, E., Chami, M., Dény, P., Kremsdorf, D., & Gordien, E. (2012) · Journal of Viral Hepatitis · doi:10.1111/j.1365-2893.2012.01597.x · Cited by 68 · see citing works
Reactive Nitrogen Species and Cell Signaling: Implications for Death or Survival of Lung Epithelium
Janssen-Heininger, Y. M. W., Persinger, R. L., Korn, S. H., Pantano, C., McElhinney, B., Reynaert, N. L., LANGEN, R. C. J., Ckless, K., Shrivastava, P., & Poynter, M. E. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.2206008 · Cited by 64 · see citing works
The Bad, the Good, and the Ugly about Oxidative Stress
Jiménez-Del-Río, M., & Velez‐Pardo, C. (2012) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2012/163913 · Cited by 64 · see citing works
Ethyl pyruvate: A novel anti-inflammatory agent
Fink, M. P. (2003) · Critical Care Medicine · doi:10.1097/00003246-200301001-00008 · Cited by 64 · see citing works
Proteolytic Response to Oxidative Stress in Mammalian Cells
Mehlhase, J., & Grune, T. (2002) · Biological Chemistry · doi:10.1515/bc.2002.057 · Cited by 61 · see citing works
Lombardi, M. S., Kavelaars, A., Penela, P., Scholtens, E. J., Roccio, M., Schmidt, R. E., Schedlowski, M., Mayor, F., & Heijnen, C. J. (2002) · Molecular Pharmacology · doi:10.1124/mol.62.2.379 · Cited by 63 · see citing works
- Authors
- Schoonbroodt, S., Ferreira, V., Best-Belpomme, M., Boelaert, J. R., Legrand-Poels, S., Korner, M., & Piette, J.
- Affiliations
- University of Liège (BE)
- Oncogenesis, Differentiation, and Signal Transduction Laboratory, Institut de Recherche sur le Cancer-Centre Nationale de la Recherche Scientifique , Villejuif ,
- Institut National de la Santé et de la Recherche Médicale, Unit 99, Hôpital Henri Mondor , Creteil ,
- AZ Sint-Jan (BE)
- Corresponding author
- Schoonbroodt, Sonia
- Piette, Jacques
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-04
- Volume
- 164
- Issue
- 8
- Pages
- 4292-4300
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1557884422
- Cited by
- 263
- References
- 66
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 8 · 2023: 6 · 2022: 9 · 2021: 9 · 2020: 13 · 2019: 6 · 2018: 9 · 2017: 7 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 13 · 2012: 10
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- ORBi (University of Liège) (submittedVersion)
- Funders
- Association pour la Recherche sur le Cancer
- Sidaction
- Fonds De La Recherche Scientifique - FNRS
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- NF-κB activation, IκBα, PEST domain, oxidative stress, hydrogen peroxide, IκBα phosphorylation, casein kinase 2, proteasomal degradation, IκB kinase, IL-1β, PMA/ionomycin, T cells, EL4 cells
- MeSH terms
- NF-KappaB Inhibitor alpha, Animals, Calpain, Cysteine Endopeptidases, DNA, DNA-Binding Proteins, Enzyme Activation, Humans, Hydrogen Peroxide, Multienzyme Complexes, Peptide Fragments, Phosphorylation, Protein Binding, Serine, Tumor Cells, Cultured, Tyrosine, NF-kappa B, Protein Tyrosine Phosphatases, Protein Serine-Threonine Kinases, Point Mutation, Protein Structure, Tertiary, Oxidative Stress, I-kappa B Proteins, Proteasome Endopeptidase Complex, Casein Kinase II, Mice, I-kappa B Kinase, Protein Tyrosine Phosphatase, Non-Receptor Type 12
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
